Constipation
Conditions
Brief summary
Chronic kidney disease is associated with the accumulation of various metabolites, i.e., uremic retention solutes. Evidence is mounting that the colonic microbiome contributes substantially to these uremic retention solutes. Indoxyl sulfate and p-cresyl sulfate are among the most extensively studied gut microbial metabolites, and are associated with cardiovascular disease, chronic kidney disease progression and overall mortality. Colonic transit time is an important determinant of intestinal generation and uptake of bacterial metabolites. However, it is unknown if accelerating the colonic transit time reduces the intestinal generation and uptake of indoxyl sulfate and p-cresyl sulfate. Prucalopride is a selective, high-affinity 5-HT4 receptor agonist with a stimulating effect on colonic motility and transit. It is currently used in treating chronic slow-transit constipation. An observational study will be initiated in non-chronic kidney disease patients with chronic slow-transit constipation necessitating treatment with prucalopride to observe its effect on serum concentrations and intestinal generation of indoxyl sulfate and p-cresyl sulfate.
Interventions
DRUGPrucalopride
Treatment with prucalopride for slow-transit constipation
Sponsors
Universitaire Ziekenhuizen KU Leuven
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 and ≤ 85 years * Chronic slow-transit constipation as defined be 4 criteria: 1. having two or fewer spontaneous complete bowel movements week for a minimum of 6 months 2. having one or more of the following symptoms for at least one-quarter of the time: lumpy/hard stools, a sensation of incomplete evacuation, or straining during defecation. 3. slow transit time as determined by Rx colon transit study (pellet) 4. without evidence of secondary constipation or primary defecation disorder * Need of therapy with prucalopride (i.e., inefficacy of dietary changes and laxatives) * Follow-up visit possible after 4 weeks of treatment * Written informed consent
Exclusion criteria
* History or new diagnosis of organic intestinal disease (e.g., inflammatory bowel disease, malignancy) * Secondary constipation (drug-induced, endocrine, metabolic or neurological disorders, surgery, known or suspected organic disorders of the large intestine, or megacolon) or primary defecation disorder * Use of laxatives two days before start of treatment and during treatment period. If there is no spontaneous bowel movement during 3 consecutive days, rescue treatment with bisacodyl and/or enema is allowed if necessary * Presence of significant co-morbidity (uncontrolled heart, liver and lung disease) * Pregnancy * Chronic kidney disease, i.e., estimated glomerular filtration rate (MDRD) \< 60 ml/min/m² or need of dialysis therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| change in serum concentration of bacterial metabolites | 4 weeks | change in serum concentration of bacterial metabolites before and after (4 weeks) treatment of prucalopride |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| change in 24h urinary excretion rate of bacterial metabolites | 4 weeks | change in 24h urinary excretion rate of bacterial metabolites before and after (4 weeks) treatment of prucalopride |
Countries
Belgium
Outcome results
None listed